#1706739 Efficacy of Teprotumumab in Phenotype Type I vs Type II Thyroid Eye Disease

Type I thyroid eye disease (TED) is typically characterized by proptosis due to expansion of the orbital fat in younger patients (pts), with absence of restrictive myopathy, and low rates of dysthyroid optic neuropathy (DON). Type II disease is characterized as presence of restrictive myopathy with higher rates of DON and diplopia and typically affects older pts. Here, we assess the efficacy of teprotumumab in pts with type I and type II TED. Teprotumumab-treated patients' data from four clinical trials were included in this post-hoc analysis. Pts with acute TED were from the phase 2 and OPTIC study with a clinical activity score (CAS)≥4 and TED duration ≤9 months; OPTIC placebo pts who were non-responders and entered OPTIC-X to receive teprotumumab were also included. Pts with longer duration TED were from the phase 4 study with TED duration ≥2 to < 10 years with CAS≤1. We assessed pts ≥40 and < 40 years of age assumed to have type I and type II TED, respectively. Baseline characteristics were evaluated. Efficacy was assessed at week 24 and included proptosis and diplopia response, proptosis least squares mean (LSM) change, and Graves' orbitopathy quality of life (GO-QOL) LSM change. Proptosis response was defined as ≥2 mm improvement. Diplopia response was defined as ≥1 Gorman grade improvement. Data from 121 pts with acute TED were included. In pts ≥40 (n=99), mean age was 54.5 years, 72.7% were female, and 74.7% had diplopia. In pts < 40 (n=22), mean age was 32.8, 59.1% were female, and 68.2% had diplopia. In pts ≥40 and < 40, 79.8% and 86.4% (P=0.602) were proptosis responders, respectively. The percentage of diplopia responders was 66.2% and 73.3%, respectively (P=0.619). Proptosis LSM change was -3.22 and -3.46 mm (P=0.525). Total GO-QOL LSM change was 15.96 and 19.09, respectively (P=0.446). Data from 42 pts in the longer duration TED trial were assessed. Of 29 pts ≥40, mean age was 56.1, 75.9% were female, 34.5% had diplopia, and 20.7% had constant diplopia. Of 13 pts < 40, mean age was 32, 76.9% were female, 30.8% had diplopia, and none had constant diplopia. LSM proptosis change was -2.60 and -2.00 mm, respectively (P=0.275). The percentage of proptosis responders was 62.1% and 61.5%, respectively (P=1). The percentage of diplopia responders was 40% and 50%, respectively (P=1). GO-QOL Appearance subscore LSM change was 8.32 and 12.95, respectively (P=0.625); Visual functioning LSM change was 8.68 and 5.00, respectively (P=0.158). Teprotumumab showed comparable efficacy in treating presumed type I and II TED in both acute and longer duration TED pts.